Method and apparatus of spectral differential phase-contrast cone-beam CT and hybrid cone-beam CT

ABSTRACT

DPC (differential phase contrast) images are acquired for each photon energy channel, which are called spectral DPC images. The final DPC image can be computed by summing up these spectral DPC images or just computed using certain ‘color’ representation algorithms to enhance desired features. In addition, with quasi-monochromatic x-ray source, the required radiation dose is substantially reduced, while the image quality of DPC images remains acceptable.

REFERENCE TO RELATED APPLICATION

This patent application is a divisional of patent application Ser. No. 13/843,508 filed Mar. 15, 2015 and allowed Mar. 11, 2016, which claims the benefit of provisional application No. 61/763,159 filed Feb. 11, 2013, and incorporates by reference the entirety of said earlier-filed applications.

STATEMENT OF GOVERNMENT INTEREST

This invention was made with government support under Grant No. R01 CA 143050 awarded by National Institutes of Health. The government has certain rights in the invention.

FIELD OF THE INVENTION

The present invention is directed to cone-beam computed tomography (CT) imaging and more particularly to phase-contrast cone-beam CT for such uses as breast imaging.

DESCRIPTION OF RELATED ART

According to the National Cancer Institute, one out of eight women will be diagnosed with breast cancer in her lifetime. And while a reduction in mortality from breast cancer is evident in published reports, each year 40,000 women will die of the disease.

The optimal breast imaging technique detects tumor masses when they are small, preferably less than 10 mm in diameter. It is reported that women with mammographically detected invasive breast carcinoma 1-10 mm in size have a 93% 16-year survival rate. In addition, as the diameter of the tumor at detection decreases, the probability of metastasis declines sharply. If a breast tumor is detected when it is 10 mm or less, the probability of metastasis will be equal to 7.31%. If a 4 mm carcinoma is detected, the metastatic probability will be decreased by more than a factor of 10, to 0.617%.

Although mammography, which on average can detect cancers ˜12 mm in size, is the most effective tool for the early detection of breast cancer currently available, mammography has relatively low sensitivity to small breast cancers (under several millimeters). Specificity and the positive predictive value of mammography remain limited owing to structure and tissue overlap. The limited sensitivity and specificity in breast cancer detection of mammography are due to its poor contrast detectability, which is common for all types of projection imaging techniques (projection imaging can only have up to 10% contrast detectability), and mammography initially detects only 65-70% of breast cancers. The sensitivity of mammography is further reduced to as low as 30% in the dense breast. Digital mammography (DM) was developed to try to overcome the limitations inherent in screen-film mammography (SFM) by providing improved contrast resolution and digital image processing; however, a large scale clinical trial, the Digital Mammographic Imaging Screening Trial (DMIST), showed that the rates of false positives for DM and SFM were the same.

The relatively low specificity of mammography leads to biopsy for indeterminate cases, despite the disadvantages of added cost and the stress it imposes on patients. Nearly 80% of the over one million breast biopsies performed annually in the U.S. to evaluate suspicious mammographic findings are benign, burdening patients with excessive anxiety and the healthcare system with tremendous cost. There is a need for more accurate characterization of breast lesions in order to reduce the biopsy rate and the false-positive rate of pre-biopsy mammograms.

To address the mammography limitations as indicated above, one of the inventors has previously developed a cone beam breast CT (CBBCT). Briefly, the major features of the prototype include a horizontal, ergonomically designed patient table with a modular insert to optimize coverage of the uncompressed breast, including the chest wall; wide openings (1 m) on each side of the patient table for easy access to the breast for positioning and potentially good access for imaging-guided biopsy and other procedures without significantly changing the basic platform; and slip-ring technology that facilitates efficient dynamic contrast imaging studies and angiogenesis imaging in the future.

The results of phantom studies indicate that CBBCT can achieve a spatial resolution up to ˜2.8 lp/mm, allowing detection of a 2 mm carcinoma and the microcalcifications ˜0.2 mm in size for an average size breast (˜13 cm in diameter at the chest wall) with a total dose of ˜5 mGy. This dose is less than that of a single mammography exam, assuming two views are required for each breast. The image quality of CBBCT for visualizing breast tissues, breast tumors and calcifications is excellent, and coverage of the breast, including the chest wall region, is at least equivalent to mammography. Visualization of major blood vessels is very good without using a contrast agent.

Ultrasound (US) is used diagnostically to distinguish fluid versus solid masses and for localization and biopsy. Lately, it has been investigated with some success to determine benign versus malignant masses through a US exam. US is a low spatial resolution study, has severe limitations in visualizing and characterizing calcifications and is highly dependent on operator skill. Intravenous dynamic contrast enhanced breast MRI (CEBMRI) currently is the only tool that provides functional information to aid in the diagnosis of breast cancer. The CEBMRI study has a high negative predictive value and near 100% sensitivity for invasive breast cancer and serves as a valuable adjunctive modality in managing the breast cancer patient once cancer has been diagnosed by other means. Because it is a tomographic study, it is currently the only breast imaging modality that is FDA approved and can truly be compared to CBBCT. CEBMRI is fully dependent on contrast resolution arising from intravenous contrast agents and the neovasculature associated with tumors. The difference in CEBMRI and all other imaging is that the image reflects contrast enhancement of vasculature rather than the actual breast anatomy. Although CEBMRI has a high sensitivity for invasive cancers, current techniques may be limited in detecting ductal carcinoma in situ (DCIS). CEBMRI is not able to distinguish calcifications and the proposed non-neovasculature involvement with DCIS, which are evident in up to 50% of breast cancers not associated with a mass.

Digital breast tomosynthesis (DBT) presently under development aims to mitigate the effect of overlapping structures. Though a measure of success has been achieved, DBT is fundamentally limited by its constraints in projection geometry; the tomographic slice is not well defined, which can cause a loss of resolution in the axial direction that affects visualization of subtle features, such as amorphous microcalcifications. CBBCT can provide isotropic high-resolution imaging of the entire breast in a more complete tomographic approach compared to other modalities, with without breast compression. It is likely to be of particular value for imaging dense breasts and breasts with implants.

As discussed above, compared to mammography including digital mammography, CBBCT has made significant advancements in detecting breast cancer. However, to accurately characterize breast tumors and calcifications and significantly reduce the biopsy rate and false positive rate of breast biopsy, it is desirable that the CBBCT should achieve a spatial resolution comparable to that of the pathology image, which is the gold standard for breast cancer diagnosis. The requirement of multifold increase in spatial resolution will mandate increasing the radiation dose over 100 times in order to maintain the same contrast-to-noise ratio (CNR) as current CBBCT. For example, if the spatial resolution is required to be increased from 2 lp/mm to 25 lp/mm, to maintain a clinical acceptable CNR, the dose level would be increased from ˜6 mGy for an average sized breast with the current CBBCT ˜186 times to 1.1 Gy. This dose increase is clinically prohibited.

The following references are considered to provide background information:

-   1. T Weitkamp, A Diaz, C David, F Pfeiffer, M Stampanoni, P Cloetens     and E Ziegler, “X-ray phase imaging with a grating interferometer,”     Opt. Express 2005; 13(16):6296-6304. -   2. G. Faris and R. Byer, “Three-dimensional beam-deflection optical     tomography of a supersonic jet,” Appl. Opt. 27(24), 5202-5212     (1988). -   3. A. Momose, W. Yashiro, S. Harasse, H. Kuwabara, K. Kawabata,     “Four-dimensional x-ray phase tomography with Talbot interferometer     and white synchrotron light,” Proc. SPIE 7804, 780405 (2010). -   R. A. Kruger and S. J. Riederer, “Basic concept of digital     subtraction angiography,” Chapter 2, pages 25-26.

SUMMARY OF THE INVENTION

It is therefore an object of the invention to achieve an increase in spatial resolution without increasing the dose to a prohibited level.

It is therefore another object of the invention to substantially reduce the x-ray radiation dose to a patient without reducing spatial resolution and contrast to noise ratio.

It is therefore another object of the invention to achieve mechanically rigid and robust implementation for a rotational-gantry system of phase contrast cone beam CT.

It is therefore another object of the invention to substantially reduce x-ray radiation dose to a patient for grating-based phase contrast cone beam CT imaging.

To achieve the above and other objects, the present invention is directed to a system and method for breast imaging or other purposes (for example, vascular imaging, pediatric cone beam CT, whole body CT imaging and interventional cone beam CT), using spectral x-ray differential phase-contrast cone beam CT that is able to record and present object information in one or more quasi-monochromatic energy channels. X-ray phase contrast cone beam CT and cone beam CT imaging as an emerging new technology will potentially achieve a spatial resolution level up to 25 lp/mm (20 μm voxel size) while maintaining an x-ray dose similar to that of the current CBBCT and mammography. In addition, since x-ray phase contrast imaging is dependent on the principles of refraction and interference of x-ray waves, more subtle information can be detected by retrieving the phase coefficients than that possible with conventional attenuation-based x-ray imaging techniques retrieving attenuation coefficients.

Conventional attenuation-based CT and cone beam CT are quite efficient in distinguishing absorption contrast between soft and hard tissues that have very different linear attenuation coefficients. However, when imaging soft tissues including breast tissues, the low absorption contrast differences of the breast structures (benign and malignant) limit its performance. Phase-contrast techniques are expected to provide an alternative way for soft tissue imaging. Unlike the principle of absorption contrast, phase-contrast imaging originates from the wave nature of x-rays, where refraction and diffraction need to be considered. As an electromagnetic wave, the x-ray is usually characterized by its wavelength, amplitude and phase. When it goes through a medium, its amplitude is attenuated, and its phase is shifted. In x-ray technology, the refraction index n of a material is usually expressed as a complex number n=1−δ+/β. The imaginary part β contributes to the attenuation of the amplitude, and the real part δ is responsible for the phase shift. It has been shown theoretically and experimentally that δ is usually more than 10³ times larger than β. Therefore, a phase contrast imaging technique will potentially provide 1000 times higher object contrast than attenuation-based CT and cone beam CT techniques.

In the past decade, various phase-contrast techniques have been developed to manifest the contrast of δ, almost all of which depend on micro-focus x-ray tubes or synchrotron radiation, which are not practical for widespread clinical applications. Recently, a new phase contrast imaging technique called the differential phase-contrast (DPC) technique has been proposed, which is a grating-based interferometry method. A high power hospital-grade x-ray tube with a wide polychromatic spectrum and high output x-ray power can be used to acquire DPC images. To further reduce the x-ray exposure, we propose a spectral DPC-based cone beam CT (DPC-CBCT) approach. One way is to shape the input x-ray as a quasi-monochromatic spectrum and thus greatly improve the dose utilization efficiency, and another way is to use an energy-resolving detector that can differentiate acquired images in several energy channels. However, it has not previously been used in the context of the present invention. This spectral DPC-CBCT approach is novel over the DPC-CBCT method, and it has not previously been used in the context of the present invention.

Related systems and methods are disclosed in the following U.S. patents: U.S. Provisional Patent Application No. 61/606,562, “Methods and apparatus for differential phase-contrast cone beam CT and hybrid cone beam CT” (Filing date Mar. 5, 2012); U.S. Pat. No. 7,949,095, “Method and apparatus of differential phase-contrast fan beam CT, cone beam CT and hybrid cone beam CT”; U.S. Pat. No. 6,987,831, “Apparatus and method for cone beam volume computed tomography breast imaging”; U.S. Pat. No. 6,618,466, “Apparatus and method for x-ray scatter reduction and correction for fan beam CT and cone beam volume CT”; U.S. Pat. No. 6,504,892, “System and method for cone beam volume computed tomography using circle-plus-multiple-arc orbit”; U.S. Pat. No. 6,480,565 “Apparatus and method for cone beam volume computed tomography breast imaging”; U.S. Pat. No. 6,477,221, “System and method for fast parallel cone beam reconstruction using one or more microprocessors”; U.S. Pat. No. 6,298,110, “Cone beam volume CT angiography imaging system and method”; U.S. Pat. No. 6,075,836, “Method of and system for intravenous volume tomographic digital angiography imaging”; and U.S. Pat. No. 5,999,587, “Method of and system for cone-beam tomography reconstruction,” whose disclosures are all incorporated by reference in their entireties into the present disclosure. The techniques disclosed in those patents can be used in conjunction with the techniques disclosed herein.

BRIEF DESCRIPTION OF THE DRAWINGS

Preferred embodiments of the present invention will be set forth in detail with reference to the drawings, in which:

FIGS. 1A-1B are graphs showing the concept of quasi-monochromatic x-ray spectrum;

FIG. 2 is a flow chart showing the idea of spectral DPC-CBCT imaging;

FIGS. 3A-3D are schematic diagrams showing a system according to a first preferred embodiment;

FIG. 4 is a flow chart showing the procedure of the phase-stepping algorithm;

FIGS. 5A and 5B are diagrams showing designs of preferred two-dimensional grating embodiments;

FIG. 6 is a schematic diagram showing a system according to a second preferred embodiment;

FIGS. 7A-7D are schematic diagrams showing a system according to a third preferred embodiment;

FIG. 8 is a schematic diagram showing a system according to a fourth preferred embodiment;

FIG. 9 is a flow chart showing a scanning protocol;

FIGS. 10A-10E are schematic diagrams showing a system according to a fifth preferred embodiment;

FIGS. 11A and 11B are schematic diagrams showing a system according to a sixth preferred embodiment;

FIGS. 12A-12E are schematic diagrams showing a system according to a seventh preferred embodiment;

FIGS. 13A and 13B are schematic diagrams showing a system according to an eighth preferred embodiment;

FIG. 14 is a diagram showing a phantom used in simulation;

FIGS. 15A and 15B are graphs showing the difference between monochromatic and polychromatic spectra in interference fringe images;

FIGS. 16A-16E are reconstructed images of the phantom for four energy channels and the combined spectrum;

FIGS. 17A and 17B are reconstructed final grayscale images; and

FIG. 18 is a reconstructed image using a color representation.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Preferred embodiments will be set forth in detail with reference to the drawings, in which like reference numerals refer to like elements or steps throughout.

Since the grating-based differential phase contrast (DPC) imaging technique using a hospital-grade x-ray tube was proposed in 2006, researchers have been quickly following up because DPC showed great potential for higher object contrast, which leads to the potential of much higher spatial resolution and dose efficiency than attenuation-based x-ray imaging. However, according to published papers, DPC imaging using a hospital-grade x-ray tube has not yet demonstrated a higher contrast resolution or better dose efficiency as expected than the attenuation-based imaging.

We have developed the DPC technology into DPC-based cone beam CT (DPC-CBCT) technology to provide three-dimensional phase coefficient of an object. According to our preliminary results, the major reason for the unexpected high dose is the polychromaticity when using a hospital-grade x-ray tube. While polychromaticity is not a major concern in absorption-based imaging, it appears as a more severe problem in phase contrast imaging because phase-contrast is much more sensitive to x-ray wavelength. In its early stage, x-ray phase-contrast imaging was limited to monochromatic spectrum by using synchrotrons coupled with single-crystal monochromators. With a polychromatic spectrum, the superposition of interference patterns generated by different x-ray wavelengths will severely degrade or even smear out the fringe contrast.

The introduction of hospital-grade x-ray tubes for grating-based DPC imaging is a smart idea to produce phase contrast using a large focal spot. While such a scheme can tolerate a quite wide x-ray spectrum, it still suffers from polychromaticity. The DPC system can only be optimized for a single x-ray energy, and the grating design and the optical setup are determined based on that ‘effective’ x-ray energy, which is usually chosen to be the peak energy in the x-ray spectrum. While the x-ray energy deviates from the optimal energy, even though the fringe pattern can still show good contrast, the fringe patterns are displaced by different amounts because the phase shift by the object is different for different x-ray energies, resulting in reduced detection contrast as the fringe patterns are summed up over the spectrum while being detected by the detector. This is similar to the dispersion phenomena in visible light. The low fringe contrast and thus the low contrast-to-noise ratio (CNR) will reduce the contrast and increase noise in the retrieved DPC images and reconstructed DPC-CBCT images. Low CNR will also cause severe phase wrapping in phase retrieval process using either the phase stepping method or the moir{tilde over (e)} pattern-based method, and if the noise is too high it is very difficult to completely correct the phase wrapping.

A preliminary study was performed through computer simulations to investigate the effect of polychromaticity. It is encouraging to see that by recording and processing DPC-CBCT in different energy channels, just the channel with the optimized energy itself (30 keV in this simulation) can provide similar image quality as that from the whole polychromatic spectrum. So rather than the entire incident x-ray exposure, a small part (40% of photon flux) with the optimal energy can do the same work. Although other non-optimal channels provide inferior image quality, they still provide spectral information of phase coefficient which can help with imaging and characterizing the object.

The simulation gives us two possible directions to improve the dose efficiency and image quality for DPC-CBCT, which leads to the idea of Spectral DPC-CBCT imaging. The first direction is to filter the incident x-ray beam into a quasi-monochromatic spectrum around the effective energy to save a significant amount of dose while producing the same image quality; the second direction is to obtain spectral information of phase coefficients in different energy channels by using a wide polychromatic spectrum to provide more information for imaging and diagnosis.

For the first direction, a quasi-monochromatic spectral can be obtained by appropriately designing the beam filter and selecting x-ray techniques. For a spectrum with a certain width where x-ray photons of all energies contribute to the imaging process, the overall output of such an imaging system, which can be either the attenuation coefficient or the phase coefficient, is usually considered as equivalent to the theoretical value corresponding to an effective energy. The effective energy is usually around the peak of the spectrum. Therefore, for either attenuation-based imaging or phase contrast imaging, it is desired to shape the spectrum as a narrow peak around the effective energy, which is often called a quasi-monochromatic spectrum. To obtain such a quasi-monochromatic spectrum around an effective energy, the following steps should be followed to filter the raw incident x-rays, and the change of spectrum is illustrated in FIG. 1A.

(1) A DPC or DPC-CBCT system is always optimized for a predefined optimal energy, based on which the gratings are fabricated and the optical geometry is set up. Choose this optimal energy as the effective energy for the spectrum.

(2) Prepare a set of metal plates that are made of different materials with different thickness. The materials include, but are not limited to, aluminum, copper, zirconium, molybdenum, tungsten, lead, iron, samarium and etc. The thickness ranges from 0.1 mm to 10 mm. Different material types have different effects in absorbing the low-energy x-ray photons, and thicker plates absorb more x-rays.

(3) Apply a combination of the metal plates to the raw incident x-ray beam and measure the filtered spectrum using a spectrometer. The tube voltage (kVp values) should be adjusted accordingly to shape the spectrum as quasi-monochromatic. The metal plates absorb the low-energy photons in the spectrum and the tube voltage shapes the high energy part. One may start with the aluminum filter with a thickness of 2-3 mm.

(4) Tube current (mA values) and pulse duration (ms values) should then be adjusted to emit sufficient x-ray photons for imaging.

A quick example of spectrum shaping is referred to reference [4], which is also shown in FIG. 1B. If a filter is designed using a 5.5 mm-thick aluminum plate, the x-rays from a tube voltage of 60 kVp can be nicely shaped into a quasi-monochromatic spectrum that is centered at ˜36 keV with a half value width of only about 15 keV Another curve in the same figure shows that a 1.5 mm aluminum plate plus a 0.2 mm samarium plate can yield a quasi-monochromatic spectrum for 60 kVp that is centered around 40 keV with a half value width of only 10 keV. According to U.S. Pat. No. 6,480,565 (Ruola Ning, “Apparatus and method for cone beam volume computed tomography breast imaging”), the optimal x-ray energy for tomographic breast imaging is 33-40 keV, which can be readily achieved using the existing beam shaping method. In the present disclosure, the spectrum shaping approach is incorporated in the novel quasi-monochromatic DPC-CBCT imaging technique, especially for breast imaging, to provide better tissue contrast and image quality by manifesting phase contrast around the optimal energy and to reduce radiation dose deposited to a patient. It is also straightforward to know that the quasi-monochromatic spectrum obtained using a beam filter can be readily used for the attenuation-based cone beam CT breast imaging technology (proposed in Ning U.S. Pat. No. 6,480,565) as well to improve tissue contrast, image quality and dose efficiency. In addition, using the same quasi-monochromatic spectrum, both attenuation-based cone beam CT and differential phase contrast cone beam CT can be obtained and combined optimally with the same scans.

For the second direction, an energy-resolving detector should be used that can record the images in different energy channels. A straightforward method is to record intensity images and optimize image processing for different x-ray energy channels. In this way, it can partially remove the “overlapping” of diffraction fringes formed by each quasi-monochromatic component. X-ray energy in each channel can be considered as a “quasi-monochromatic” component of the spectrum if the channel is narrow. For practical considerations, each channel should also be wide enough to contain sufficient x-ray photon flux and to accommodate to energy threshold configurations of the energy-resolving detector. Although compared to regular DPC imaging, each channel will have fewer photons and thus the quantum noise in the recorded intensity images will be higher, the noise level in the DPC image in that channel should not be too high because the fringe contrast, rather than the quantum noise, is the dominant factor in determining the noise level in the retrieved DPC images. Therefore, it is possible to obtain diffraction images, DPC images and DPC-CBCT reconstructions at different energy levels, and the resulting “composite” information can be combined using appropriate algorithms to maximize the final object information by ‘coloring’ imaging and display. Meanwhile, as image processing is optimized based on the specific x-ray energy in that channel, the performance of each energy channel can be maximized and the utilization of the x-ray dose can be greatly improved.

The idea of spectral DPC-CBCT imaging is illustrated in FIG. 2. From a four-channel x-ray spectrum 1100, spectral DPC images 1102-1 through 1102-4 from channels 1 through 4, respectively, are taken. From each spectral DPC image 1102-1 through 1102-4, a spectral DPC-CBCT reconstruction image 1104-1 through 1104-4 is reconstructed. From those reconstructed images 1104-1 through 1104-4, a comprehensive representation 1106 of spectral DPC images or DPC-CBCT reconstruction images is formed.

An energy-resolving detector is generally a photon-counting detector, and a good example is Medipix 3, which is the 3rd generation detector in the Medipix family developed by European Center for Nuclear Research (CERN, Genéve, Switzerland). It is a CMOS photon-counting detector that takes images based on the number of particles which hit the pixels when the electronic shutter is open. It has a spectroscopic mode that permits either four separate thresholds (two channels) in simultaneous read/write mode or eight thresholds (four channels) in sequential read/write mode. Medipixel 3 is designed for 5-50 keV, which fits the spectrum used in our DPC-CBCT system. Each Medipix 3 chip has a pitch of 55 μm (no binning), a matrix of 256×256, a dynamic range of 16,000:1 (14 bits) and a total active area of 1.4 cm×1.4 cm. Larger area coverage can be achieved by seamlessly connecting multiple Medipix3 chips by three sides (the only side that is left connects to the readout circuits), which could reach a coverage of 2.8 cm×1.4 n cm (n is an integer), and, given the current nanofabrication technologies, there is no major technical difficulty to enlarge the active area of a single Medipix 3 chip, which could be another possibility to enlarge the active area in the future.

For the purpose of high resolution medical imaging and especially for breast imaging using the proposed spectral DPC-CBCT approach, an energy-resolving detector should be designed and constructed according to the specifications of the existing Medipix3 detector.

The major parameters of such a new detector are listed in Table 1.

TABLE 1 Major specifications of a desired energy-resolving detector Detector pitch 25-1000 μm Spatial resolution 2.5 lp/mm-25 lp/mm Frame Rate 0.5 fps-1000 fps Active area 2.8 cm × 2.8cm-50 cm × 50cm Energy response 5-50 keV Thresholds at least 8 thresholds per pixel (four energy channels) Dynamic Range >16,000:1

Either the phase stepping method or the moir{tilde over (e)} pattern method can be combined with the two new directions as described above to perform spectral DPC and spectral DPC-CBCT imaging. The detailed information will be disclosed later in the context of preferred embodiments.

A first preferred embodiment is directed to a quasi-monochromatic differential phase-contrast cone-beam CT system (DPC-CBCT) for in vivo clinical imaging using a quasi-monochromatic spectrum. As shown in FIGS. 3A-3D, such a spectral DPC-CBCT system 100 includes a hospital-grade x-ray tube 102 coupled with a beam filter 103, a source grating 104, a high-resolution detector 110 and a phase-analyzer grating pair 122 mounted on a gantry 112. The beam filter is designed using a combination of metal plates according to the approach described above. It should be noted that the beam filter design is different for a filter that is placed before the source grating and a filter that is placed after the source grating, because the silicon substrate in the grating may also shape the x-ray spectrum to some extent.

The phase stepping method can be used to manifest the phase contrast and to retrieve the phase information, where any of the source grating 104, the phase grating 106 or the analyzer grating 108 can be stepped to apply the phase stepping method.

When the source grating 104 is stepped, the stepping mechanism can be designed either as the linear stage-based mechanism in FIG. 3A or the dial source grating system 120 as in FIG. 3B. In FIG. 3A, a motor-driven stage 116 moves the source grating 104 to produce different phase steps. The object O will be kept stationary while the gantry will be rotating to take images during a scan. A computer 118 controls the operations of the system and analyzes the data. For the purpose of high resolution imaging, it is required to accurately synchronize the performance of all the system components. A synchronizer 140 synchronizes the timing of gantry rotation, phase stepping (by linear stage or branch dial), x-ray pulse, and data acquisition to make full use of x-ray exposure for imaging, achieve the required mechanical accuracy and precision and minimize the total scan time. The purpose of the source grating system 120 in FIG. 3B is to produce different phase steps that are defined as relative displacements in the direction perpendicular to grating lines between the source grating 104 and the phase-analyzer grating pair 122 which is composed of a phase grating 106 and an analyzer grating 108. Grating system 120 is composed of several branches and at each branch, a source grating is fixed. The grating system is designed in such a way that when each branch is aligned with the phase-analyzer grating pair, the relative displacement between the source grating and the phase-analyzer grating pair ranges from a small fraction of the period of the source grating 104 to one grating period across different branches.

When either the phase grating 106 or the analyzer grating 108 is stepped, the stepping mechanism can be designed either as the linear stage-based mechanism in FIG. 3C or the dial source grating system 120 as in FIG. 3D. The purpose of the grating system is to produce different phase steps that are defined as relative displacements between the phase grating 106 and the analyzer grating 108 in the direction perpendicular to grating lines. In FIG. 3C, the analyzer grating is stepped using a motor-driven linear stage 116 to produce a set of different lateral displacements with respect to the phase grating, and a set of phase stepping images are acquired to retrieve the phase information. Similarly, the linear stage 116 can be also mounted under the phase grating 106 to produce the same effect. In FIG. 3D, the grating system 120 is composed of several branches and at each branch, a phase grating 106 and an analyzer grating 108 are fixed. The relative displacement between the phase grating 106 and the analyzer grating 108 ranges from a small fraction of the period of the analyzer grating 108 to one grating period across different branches. By successively aligning each branch to the optical axis, a set of phase stepping images can be acquired to retrieve the phase information.

A synchronizer 140 control and synchronize the operation of x-ray source, detector, gantry and gratings to perform the imaging process. A computer 118 performs system configuration, data acquisition, three-dimensional tomographic reconstruction and data analysis.

The DPC technique is able to produce one-dimensional or two-dimensional spatial coherence by applying an absorption grating (the source grating 104) to a high power x-ray tube 102 that has a focal spot size of hundreds of microns and a high x-ray output power (>10 kW). The line patterns 114 made of high atomic number materials of the source grating 104 can absorb almost all x-ray photons impinging on them while the grooves in between let all the x-ray photons pass through. The width of the grooves is designed to be comparable to the focal spot size of a micro-focus x-ray tube. Thus the source grating divides a large focal spot x-ray source into several narrow line sources. Each of those line sources is able to produce sufficient spatial coherence at the direction perpendicular to the lines, while they are mutually incoherent. When proper parameters are chosen, those line sources contribute constructively in the imaging process. In a similar manner, the grating pattern can be designed as a matrix of multiple pinholes and each pinhole functions as a point source that is able to individually provide sufficient coherent length in both dimensions but mutually incoherent.

The phase-stepping algorithm [1] is used to calculate each DPC image, the physical principle of which is briefly explained as following: The phase grating 106 shows negligible absorption but substantial phase shift, dividing the x-ray beam into two first diffraction orders. The refracted beams then interfere and form periodical fringes at an integer or fractional Talbot distance where the analyzer grating 108 is placed. The period of the analyzer grating is chosen to be the same as the period of the fringes. If the incident x-ray beam encounters an object before it reaches the phase grating, its wavefront will be perturbed by the object, leading to local displacement of the fringes. The phase stepping algorithm can be used to retrieve the encoded phase information based on detector images. An x-ray detector with a pitch larger than the diffraction fringe period can be used to record the intensity images, which removes the restriction of an ultrahigh detector resolution that has a pitch even smaller than the diffraction fringes. In principle, while any of the three gratings (source grating 104, phase grating 106 and analyzer grating 108) is stepped, the detected intensity value of any pixel in the detector is modulated by the position of the stepped grating. If the modulation function is transformed into the Fourier domain, then the complex angle of the first Fourier component is the first derivative of phase at this pixel. The DPC image of an object acquired in that way is a raw DPC image. Usually the background phase distribution due to the non-uniformity of the grating system is acquired by the same process without an object in place, and the true DPC image of the object is acquired by subtracting the background phase distribution from the raw DPC image.

The whole procedure is shown in FIG. 4. Without the object in place, in steps 1000-1 through 1000-M, background DPC images are taken at phase steps 1 through M. Pixel-wise calculations are performed in steps 1002 and 1004. With the object in place, in steps 1006-1 through 1006-M, raw DPC images are taken at phase steps 1 through M. Pixel-wise calculations are performed in steps 1008 and 1010. The final pixel-wise calculation in step 1012 calculates the final image from the DPC raw and background images.

It should be noted that the background information can be pre-stored for the background correction for a given DPC system, and therefore it is not necessary to be acquired for every scan. In addition, an attenuation image can be obtained by summing up the phase stepping images to produce absorption contrast, and a dark-field image can be obtained by calculating the ratio of the first Fourier component and the zeroth Fourier component to produce the contrast due to small-angle scattering caused by sub-micron structures.

The DPC images acquired from all view angles will be directly used for reconstruction instead of calculating the line integrals of phase coefficient first from the DPC images. Considering that the cone angle of the DPC-CBCT system is small, the parallel beam approximation can be applied for tomographic reconstruction, and a filtered backprojection (FBP) algorithm with Hilbert filtering can be used [2]. The DPC images are row-wisely filtered using the Hilbert filter, and then are backprojected into the object space to calculate the 3-D distribution of the linear phase coefficient. When the object is fully covered by the x-ray beam at all view angles (no transverse truncation), the reconstruction result is accurate up to a constant. The reconstruction constant can be easily determined by setting the phase coefficient of surrounding air to zero. In the case of volume-of-interest (VOI) imaging where truncation occurs, this reconstruction method also works, but the image quality will be degraded by the background trend, and the reconstruction constant has to be determined using prior knowledge of the object. Besides, backprojection-filtration (BPF) algorithms can be modified for DPC-CBCT reconstruction because a differentiation operation is usually performed before backprojection while the DPC image is very similar to the intermediate result after the differentiation operation. This type of algorithm also has a good capability to handle severe truncations. The procedure of DPC-CBCT imaging using a typical BPF reconstruction comprises the same methods to obtain DPC images, and the only difference is the reconstruction quantity. The major steps are: (a) acquire raw intensity data from all view angles; (b) compute DPC images using the phases-stepping algorithm from the intensity data as shown in FIG. 2; (c) backproject the DPC images to the object space from all view angles; and (d) filter the backprojected data using desired filter(s) along specified direction(s). The projection images can be attenuation images, DPC images and dark-field images, and the reconstructed quantity are then respectively the attenuation coefficient, phase coefficient and density of sub-micron structures.

In the present disclosure the one-dimensional grating system with the corresponding scanning protocol and reconstruction algorithm is discussed in detail. It should be noted that it is straightforward to extend the one-dimensional grating system into a two-dimensional system where the source grating is composed of multiple point sources while the phase grating and the analyzer grating are composed of two-dimensional matrices. Some of the possible embodiments are shown in FIGS. 5A and 5B as 1302, 1304, 1306, and 1308.

The phase-stepping algorithm should be performed in preferred directions (x, y, diagonal and etc) to extract the phase contrast equally in both x and y directions. A modification should be carried out for the cone beam reconstruction algorithm to deal with the phase gradient in both directions.

Major parameters of the proposed DPC-CBCT system are listed in Table 2. A hospital-grade x-ray is used for the DPC-CBCT system. The x-ray tube has a focal spot size of 0.05 mm to 2 mm and an output power of several kilowatts to tens of kilowatts. It will operate at 10 kVp to 150 kVp. Generally it can be any kind of diagnostic imaging x-ray radiation sources, including mammography tubes, angiography tubes, CT tubes and other general purpose radiographic tubes, depending on the clinical applications.

TABLE 2 Major system parameters Focal spot size 0.05 mm-2 mm Peak voltage 10 kVp-150 kVp Detector pixel size 10 μm-1000 μm Detector frame rate 0.5 fps-1000 fps Detector dimensions 3 cm × 3 cm-50 cm × 50 cm Gantry rotation speed >0.5 RPM Detection Quantum Efficiency >50% (DQE) of detector Dynathic Range >30,000:1 The system spatial resolution >2.5 lp/mm-25 lp/mm

A two-dimensional detector is used for the DPC-CBCT system. Unlike other phase-contrast imaging techniques, there is no strict requirement for an ultra high resolution detector, and the detector resolution can be ˜10 μm-1000 μm, determined by the applications and expected image resolution. The frame rate of the detector is 0.5 frames per second (fps) to 120 fps for different image acquisition protocols. For the potential application of breast imaging which requires high spatial resolution and high contrast resolution, the detector should have a detection quantum efficiency (DQE) of >50% and a dynamic range of >30,000:1. The system spatial resolution is expected to be over 2.5 lp/mm-25 lp/mm.

The source grating is mounted as close to the focal spot as possible for the best field of view. It divides the x-ray beam into many line sources, and the width of each line source is generally less than 50 μm to provide sufficient spatial coherence. The phase grating is mounted right behind the object and yields a phase difference of PI between grooves and ridges. The period of the phase grating is 2 μm to 8 μm. The analyzer grating is mounted right at the surface of the detector, and it attenuates x-rays to 20% to 80% at grooves by strongly attenuation materials. The period of the analyzer grating is the same or half of that of the phase grating (up to a magnification factor which is close to 1.0), depending on the distance between the two gratings, which can be fractional Talbot distances or integer Talbot distances. The distance between the source grating and the phase grating and the distance between the phase grating and the analyzer grating determine the period of the source grating, which is usually 30 μm to 200 μm. The sizes of the gratings are designed to cover the field of view for the specific applications of the DPC-CBCT system. Major grating parameters are listed in Table 3. A possible variation would use two-dimensional phase contrast gratings. It should be noted that such a grating design is ideal for parallel x-ray beam or an x-ray beam with small cone angle as the grating grooves are parallel. When a larger cone angle (>5 deg) is used, it would be better to use focused gratings that are designed and fabricated with consideration of the diverging x-ray beam.

TABLE 3 Major grating parameters Source Phase Analyzer grating 104 grating 106 grating 108 Grating pitch 30-200  2-8 Same or half p (μm) that for phase grating 106 Groove height 40-200 10-50 (phase 10-100 t (μm) shift of PI) Duty cycle Line width < 50% 50% 50 μm

The x-ray tube, detector and grating system are mounted on a rotation gantry that can achieve a speed of 0.5 revolutions per minute (RPM) to 60 RPM or larger. The object or patient is kept stationary during a scan.

In the proposed DPC-CBCT technique, the data acquisition geometry is not limited to the circle orbit. The gantry can be controlled and moved by at least one motor to perform scans along various orbits, including a spiral geometry, a circle-plus-line geometry and a circle-plus-arc geometry.

The second preferred embodiment is a variation of the first preferred embodiment where instead of the phase stepping method, the moir{tilde over (e)} pattern method is used to manifest and retrieve the phase information. The major advantage of the second preferred embodiment is that all the information can be obtained through a single moir{tilde over (e)} pattern image, and no stepping is required. That reduces the complexity of image formation and makes fast imaging possible. As shown in FIG. 6, the second preferred embodiment has the same system components as that of the first preferred embodiment in FIG. 3A except that the linear stage is removed. In the system 200, the beam filter 203 is coupled to the x-ray tube to provide quasi-monochromatic x-ray spectrum. The phase grating 206 and analyzer grating 208 are slightly misaligned to produce the moir{tilde over (e)} pattern, which is distorted with the presence of an object in the x-ray beam as a result of phase change. By analyzing the moir{tilde over (e)} pattern using a Fourier transform approach, it is possible to retrieve the attenuation image from the zeroth Fourier component, the differential phase contrast (DPC) image from the first Fourier component and the dark field image from the ratio of the previous two. The reconstruction algorithms as described before can be used to reconstruct the 3D phase coefficient using the retrieved DPC images.

It should be noted that the analyzer grating 208 does not have to be an attenuation grating as that for the second embodiment. Instead, it could be a second phase grating that produces significant phase change but negligible amplitude change. A phase-phase grating pair will also produce similar moir{tilde over (e)} patterns if the detector is placed at an appropriate location, which could be a fractional Talbot distance or an integer Talbot distance.

The third preferred embodiment is a variation of the first preferred embodiment where the beam filter 103 is removed and the detector is an energy-resolving detector 130. Such a system works in the same way as the first preferred embodiment except that by recording images in different energy channels, it can perform spectral DPC and spectral DPC-CBCT imaging as described in the second direction. This embodiment is shown in FIGS. 7A-7D.

The fourth preferred embodiment is a variation of the second preferred embodiment where the beam filter is removed and the detector is an energy-resolving detector. Such a system works in the same way as the second preferred embodiment except that by recording images in different energy channels, it can perform spectral DPC and spectral DPC-CBCT imaging as described in the second direction. This embodiment is shown in FIG. 8.

The present invention allows the implementation of a DPC-CBCT system to detect and characterize breast tumors and micro-calcifications with a spatial resolution up to 25 lp/mm, which is comparable to that of pathology images and results in the significant reduction of biopsy rate. The following design considerations are involved. The first design consideration is to design and construct a coherent x-ray radiation source that combines the hospital-grade x-ray tube with a specially designed and constructed grating (104) to provide a stable coherent radiation source with 5 cm field of view (FOV) coverage or larger. The second design consideration is to fabricate high quality gratings with uniform microstructures to cover the proposed FOV. The third design consideration is to design and construct an appropriate 2D detector system which has ultra-high spatial resolution (˜20 μm/detector cell), a high detective quantum efficiency (DQE), high dynamic range, minimal geometric distortion and excellent linearity. For the third and the fourth embodiments, this detector should also have good energy resolving capability. The fourth design consideration is to develop a practical DPC-CBCT data acquisition scheme along with accurate and efficient phase stepping algorithms and DPC-CBCT reconstruction algorithms. The fifth design consideration is to design and construct the proposed HBCT (hybrid breast CT) system (CBBCT plus DPC-CBCT) to ensure a targeting DPC-CBCT scan and proper coverage of the volume of interest.

As discussed above, the requirement for a phase contrast imaging system is that the incident x-ray beam should be spatially coherent to a certain degree, and it is possible to perform DPC-CBCT imaging using high power hospital-grade x-ray tubes with an attenuation grating. To meet this challenge, we propose to select a high-power mammography tube or general radiography tube with an anode power larger than 10 kW and couple it with a specially designed source grating 104, where the x-ray tube can be considered as being divided into many narrow line sources with width of 10-50 μm, and these line sources are individually spatially coherent in the direction perpendicular to grating grooves but mutually incoherent. With this design, the source is able to provide sufficient x-ray flux even with the strong attenuation of the source grating. The high aspect ratio (the ratio between groove height and groove width) of the grating 104 may affect the field of view, and it is important to mount the grating 104 as close to the focal spot as possible (preferably <1 cm) for larger FOV.

The gratings used for DPC-CBCT imaging will be fabricated using Micro-Electro-Mechanical Systems (MEMS) nanofabrication facilities, including photolithography, physical etching, chemical etching, deposition and electroplating. The major challenge is the high aspect ratio of the gratings (the ratio between groove height and width), which makes etching and electroplating difficult. For the phase grating and the analyzer grating, the aspect ratio can be as high as 15 to 40, which causes difficulties in etching with straight edges or growing gold into deep grooves. To solve this issue, a high-quality <110> orientated single crystal silicon substrate (Nova Electronic Materials, Flower Mound, Tex.) will be used that is highly selective in a preferred direction, with which it is easier to form sharp and deep edges by wet etching using potassium hydroxide (KOH). A nitride layer will be used as the mask and the atomic layer deposition (ALD) will be used to epitaxially grow the seed layer of gold. Next, electroplating will be used to grow the gold layer on top of the seed layer following its own crystal structure. Other elements with high atomic numbers, like Pt, Hf or Ta, can be used as well. Currently the standard large scale MEMS technique is limited to silicon wafers with a diameter of 4 inches, but it is expected to achieve much large silicon wafer size and also grating size in the future. In addition, wafers with small thicknesses will be used to reduce the unnecessary x-ray attenuation of any grating and to reduce the x-ray exposure to patients,

Most of the currently available detectors for hard x-rays, including thin film transistor flat panel detector (TFT-FPD), charge-coupled device (CCD) detector, and complementary metal-oxide-semiconductor (CMOS) detector, can be used. Appropriate scintillators should be chosen for the best x-ray energy response. However, for the purpose of breast imaging, which concerns the small size of microcalcifications (as small as 0.2 mm) and low contrast resolution among soft tissues, some special requirements should be specified. The detector should have a dynamic range of >30,000:1 (or >16 bit A/D conversion), a detective quantum efficiency (DQE) of >50% and a spatial resolution of the system should be 2 lp/mm-25 lp/mm. The system can have isotropic spatial resolution. A higher frame rate of 0.5 fps-1000 fps is expected that makes it possible to achieve a faster scanning process and reduced motion artifacts. Besides those features, energy-resolving capability is required for the third and the fourth preferred embodiments. It can be a photon-counting detector that takes images based on the number and energy of particles which hit the pixels according to preset thresholds.

The conventional CBCT scanning protocol is quite straightforward, as only one x-ray exposure is needed to acquire an absorption image at each view angle. The second and the fourth preferred embodiments can perform in the same way as a conventional CBCT scan as no stepping is needed. The first and the third preferred embodiments, however, require at least three x-ray exposures at any view angle, and one of the gratings will be shifted to a different position for each exposure to acquire the phase-stepping images, which will then be processed to compute the final images (attenuation, DPC, or dark-field) at that view angle. Thus the phase-stepping algorithm for phase retrieval adds more complexity in the DPC-CBCT scanning protocols. A straightforward scanning scheme is to use the step-and-shoot method, where all the phase stepping images are acquired sequentially when the gantry stops at each view angle. The gantry rotates and stops at each view angle, and during each stop period, the branch dial grating system rotates to align each branch to the optical axis, the x-ray system shoots and the detector acquires an image. That approach also works for the linear stage-based grating system where the linear stage shifts and aligns the gratings during each stop period. To improve the efficiency, the rising edge of the x-ray pulse should occur immediately after the aligning action is completed by either the branch dial or linear stage which can be precisely controlled by the Synchronizer. This approach can minimize object motion when acquiring the phase stepping images at each view angle, but the total scanning time might be longer because of the step-and-shoot scheme. Another scanning scheme is to divide a complete DPC-CBCT scan into several sub-scans, the branch grating system being rotated to the next branch (FIGS. 3B, 3D, 7B and 7D) or the grating being shifted by the linear stage (FIGS. 3A, 3C, 7A and 7C) before each sub-scan but fixed during each sub-scan. This scheme can reduce the total scanning time because it allows the gantry to continuously rotate. Then the phase-stepping algorithm will be performed to calculate the DPC images at each view angle, and the reconstruction algorithm will be performed to calculate the tomographic images. Assuming that M phase-stepping images (M≥3) are needed to calculate the DPC image at each view angle and N DPC images are needed for tomographic reconstruction, the whole scanning process is illustrated in FIG. 9. The shifted grating (any of the three gratings or the branch grating system) is positioned in a plurality of steps 602-1, 602-2, . . . , 602-M in a plurality of positions; between those steps, it is repositioned in step 604. When the shifted grating is in each of the positions, a scanning step 606-1, 606-2, . . . , 606-M is performed to take an image set. The scans result in a DPC image set in step 608, which is reconstructed in step 610. Either the FBP-type or iterative-type reconstruction algorithm can be used for reconstruction, and the compressed sensing-based iterative algorithm can be applied to further reduce image noise or reduce required dose while maintaining image quality which is clinically acceptable. Phase wrapping due to large phase derivatives or high noise level in intensity images is the major problem that may cause false phase information in DPC images, appearing as discontinuities. This problem will be solved by detecting singularities based on wavelet analysis and correcting singularities by interpolation.

High precision, good stability and accurate alignment are required in construction and calibration of the DPC-CBCT system, which concern mostly the position of the three gratings that are aligned along the optical axis. They should be mechanically stable down to a scale of approximately one-tenth of its grating period (approximately 3-20 μm). The similar scale of stability also applies to the precision of each step, which can be a rotation or a transverse motion. Another concern is that the relative position of the phase grating and the analyzer grating should be stabilized. The grating mounts will be equipped with precise one-way translation and three-way rotation to make the gratings 106 and 108 well aligned with their grooves parallel to each other, or to make the gratings 206 and 208 misaligned by a desired small angle. The angular sensitivity of grating mounts is expected to be within a couple milliradians to minimize a possible moir{tilde over (e)} pattern for the phase stepping method or to generate a desired moir{tilde over (e)} pattern for the moir{tilde over (e)} pattern method. As the gantry will be rotated during a scan, it is a mechanical challenge to stably rotate the source-detector set while keeping the relative position between the tube, the detector and the grating system unchanged with an accuracy of a few microns.

Large-scale fabrication techniques with silicon wafers are under development that are able to make gratings as large as 30 cm×30 cm. The advance of MEMS techniques may also make it possible to make two dimensional gratings that are able to show phase contrast equally well in both directions and eliminate the possible problems with object orientation. There are no major technical obstacles in fabrication of large-area (up to 50 cm×50 cm), high-resolution (>25 lp/mm) detectors using CMOS or CCD techniques, and the frame rate is expected to be improved by tens of times with novel parallel acquisition and fast caching techniques. Hence, the field of view will be greatly enlarged for ultrahigh resolution breast imaging or whole body imaging. Though the x-ray tube is not a limitation for DPC imaging, emerging techniques of compact micro-focus x-ray tubes, including laser plasma tubes and liquid metal target tubes will further improve image resolution and simplify the system design by removing the grating 104 that may increase field of view and improve exposure uniformity.

With the technique advances described above, the spectral DPC-CBCT imaging system is expected to scan faster (achieve a few seconds/scan), cover larger objects, and provide higher spatial resolution, which makes it possible to use the DPC-CBCT imaging as both screening and diagnosis tools. The screening DPC-CBCT system will be designed with a lower spatial resolution (˜100-75 μm) and the patient will be exposed with very low exposure (lower than that of two view screening mammography). The diagnostic DPC-CBCT system will be designed with a higher spatial resolution (˜50-20 μm) and the patient dose will be equivalent to that of a diagnostic mammography (˜6 mGy for average size normal density breast). Currently the VOI breast imaging is designed as a hybrid system with two sub-systems: a CBCT system and a DPC-CBCT system. In the future it can be further simplified as a single DPC-CBCT imaging system that can perform both a screening scan and a diagnostic VOI scan by switching the field of view, different resolutions (standard resolution for large field view and screening imaging and ultrahigh resolution for small field and diagnostic imaging) and different readout rates (0.5 frame/s-120 frame/second).

Our first application of the proposed DPC-CBCT technique is a cone beam breast CT modality for breast cancer diagnosis to reduce the biopsy rate; however, the technology can be also used for whole body imaging as well as angiography and bone imaging.

A fifth preferred embodiment combines current cone beam CT with spectral DPC cone beam CT to form a hybrid cone beam CT that is capable of acquiring both 3D high resolution cone beam CT imaging and ultrahigh resolution DPC-cone-beam CT imaging. FIG. 10A shows the cone beam CT breast imaging system as disclosed in U.S. Pat. No. 6,480,565 “Apparatus and method for cone beam volume computed tomography breast imaging” (Ning '565), and the hybrid cone beam CT system is supposed to replace the cone beam CT system beneath the patient table to perform hybrid breast imaging. FIGS. 10B, 10C, 10D and 10E show one possible design for a hybrid cone-beam CT system 500 for breast imaging by combining the first preferred embodiment with the cone beam CT technology. The system 500 includes a current cone beam breast CT (CBBCT) system, which is mainly composed of

an x-ray tube 520 and a flat-panel detector 522 such that the CBBCT imaging chain images the breast only using a half-cone geometry in which x-ray radiation radiates the breast only without penetrating chest cavity or other body parts of the patient, resulting in substantially reduced radiation to the patient. On the same rotary gantry 524, a quasi-monochromatic DPC-CBCT system is constructed which is one of the four sub-types of the first preferred embodiments as shown in FIG. 3B-3E. The CBBCT is used to scan the whole breast B first and find out the 3D location of any suspicious volume; the breast is then translated and positioned such that the suspicious volume is centered in the field of view (FOV) of the DPC-CBCT system; finally the DPC-CBCT system performs an ultrahigh-resolution scan of a region of interest (ROI), and the phase coefficient of the 3D volume is reconstructed. This ultrahigh-resolution DPC-CBCT scan is expected to reveal ducts (<0.25 mm in width), small vessels (<0.5 mm in width) and microcalcifications (<0.2 mm in diameter) for diagnosis and treatment of breast cancers.

It is also straightforward to apply the beam filter to the attenuation-based CBCT imaging chain in the hybrid system to further improve tissue contrast, image quality and dose efficiency for CBCT.

Studies have shown that while DPC-CBCT outperforms in most cases, attenuation-based CBCT is more sensitive in imaging certain materials and soft tissues. Therefore, the hybrid system can utilize the advantages of both DPC-CBCT and attenuation-based CBCT to provide complimentary information in medical imaging and breast imaging. In addition, using the same quasi-monochromatic spectrum in the hybrid system, both attenuation-based cone beam CT and differential phase contrast cone beam CT can be obtained and combined optimally with the same scans.

The sixth preferred embodiment is a variation of the hybrid system as shown in FIG. 11. FIG. 11A shows the cone beam CT breast imaging system as disclosed in U.S. Pat. No. 6,480,565 “Apparatus and method for cone beam volume computed tomography breast imaging” (Ning '565), and the hybrid cone beam CT system is supposed to replace the cone beam CT system beneath the patient table to perform hybrid breast imaging. FIG. 11B is actually a combination of the moir{tilde over (e)} pattern-based system (second preferred embodiment) and the current CBBCT system. The CBBCT system images the breast only using a half-cone geometry in which x-ray radiation radiates the breast only without penetrating chest cavity or other body parts of the patient, resulting in substantially reduced radiation to the patent. It should be noted that as no stepping is required in the system 600, it can perform fast data acquisition, which makes dynamic imaging possible using this system.

The seventh preferred embodiment is a variation of the hybrid system as shown in FIG. 12. FIG. 12A shows the cone beam CT breast imaging system as disclosed in U.S. Pat. No. 6,480,565 “Apparatus and method for cone beam volume computed tomography breast imaging” (Ning '565), and the hybrid cone beam CT system is supposed to replace the cone beam CT system beneath the patient table to perform hybrid breast imaging. FIGS. 12B, 12C, 12D and 12E are actually combinations of the phase stepping-based spectral DPC-CBCT system using an energy-resolving detector (the third preferred embodiment) and the current CBBCT system. The CBBCT system images the breast only using a half-cone geometry in which x-ray radiation radiates the breast only without penetrating chest cavity or other body parts of the patient, resulting in substantially reduced radiation to the patient.

The eighth preferred embodiment is a variation of the hybrid system as shown in FIG. 13. FIG. 13A shows the cone beam CT breast imaging system as disclosed in U.S. Pat. No. 6,480,565 “Apparatus and method for cone beam volume computed tomography breast imaging” (Ning '565), and the hybrid cone beam CT system is supposed to replace the cone beam CT system beneath the patient table to perform hybrid breast imaging. FIG. 13B is actually a combination of the moir{tilde over (e)} pattern-based spectral DPC-CBCT system using an energy-resolving detector (the fourth preferred embodiment) and the current CBBCT system. The CBBCT system images the breast only using a half-cone geometry in which x-ray radiation radiates the breast only without penetrating chest cavity or other body parts of the patient, resulting in substantially reduced radiation to the patient.

It should be noted that all the eight embodiments can be performed in a spiral scan mode to increase the coverage by moving the object along the rotation axis while the gantry is rotating. There are no theoretical or mechanical difficulties for this application extension.

The mathematical model of DPC imaging using a polychromatic spectrum will now be discussed. To model a polychromatic imaging process, the final intensity image should be integrated over the entire imaging process. The complex amplitude for a specific wavelength λ is expressed in Equation (1), and the diffraction image using a polychromatic spectrum is shown in Equation (2). The notations include U₀ for the incident complex amplitude, U for the complex amplitude at the detector plane, T_(obj) for the transmission matrix of object, T_(G1) for the transmission matrix of the phase grating, T_(G2) for the transmission matrix of the analyzer grating, H for the Fresnel kernel and l for the intensity imaging acquired by the detector. Major simulation parameters are listed in Table 4. U(λ,x,y)=(U ₀(λ,x,y)·T _(obj)(λ,x,y)·T _(G1)(λ,x,y))

H(R;λ,x,y)·T _(G2)(x,y)  (1) I(x,y)=∫(U(λ,x,y)·U*(λ,x,y))dλ  (2)

TABLE 4 Simulation parameter selection Source-to-Object distance 1.0 m Detector pitch  64 μm Phase grating pitch   4 μm Analyzer grating pitch   2 μm Number of phase steps  4 Basic simulation unit 0.5 μm Number of projections 360

As the Medipix 3 allows eight thresholds to define four channels in its spectroscopic mode, we assume the x-ray spectrum is divided into four channels and each channel contains a certain percentage of the total incident x-ray photons. Each channel is represented using its center energy, including 20 keV (20%), 30 keV (40%), 40V (25%) and 45 keV (15%). The optical setup of the DPC-CBCT system is optimized for 30 keV.

The phantom is composed of a water cylinder (8 mm in diameter) with four rod inserts (2 mm in diameter). The layout is shown in FIG. 14, and the coefficients are listed in Table 5. For convenience, the assigned phase coefficients are normalized to the phase coefficients of water at 30 keV, which is 3.7175×10⁴ m⁻¹ according to the NIST database and the Klein-Nishina formula.

TABLE 5 Phase coefficients for the numerical phantom (normalized to the phase coefficient of water at 30 keV) A (water) B C D E 20 keV 1.20 1.26 1.32 1.38 1.44 30 keV 1.00 1.05 1.10 1.15 1.20 40 keV 0.90 0.945 0.99 1.035 1.08 45 keV 0.80 0.84 0.88 0.92 0.96

For fair comparison, the reconstruction is expressed in “CT Numbers” that is defined in a similar way as that for attenuation-based CT. The phase coefficient of water is the theoretical number as defined in the simulation, and the CT number for each energy channel is calculated using the phase coefficient of water for that energy channel. The expression is shown as Equation (3).

$\begin{matrix} {{CTNumber} = {1000 \times \frac{\varphi - \varphi_{water}}{\varphi_{water}}}} & (3) \end{matrix}$

FIGS. 15A and 15B demonstrate the difference between a monochromatic spectrum and a polychromatic spectrum for DPC imaging. Both figures are profiles of fringe displacement in a self image due to phase shift of an object, where the incident x-rays have a unit intensity. The monochromatic spectrum has an energy of 30 keV, while the polychromatic spectrum is designed as above. Assume the phase shift is 0.0625π for 20 keV, 0.125π for 30 keV, 0.1875π for 40 keV and 0.25π for 45 keV due to their different wavelength and phase coefficients. The normalized contrast of monochromatic fringes is close to 2.0 (2.0 vs. 0) while the contrast of polychromatic fringes is averagely 1.3 (1.6 vs. 0.3), which is 35% lower and thus more vulnerable to noise and phase wrapping. It is obvious that the shape of the polychromatic fringe is no longer a square wave, and the shape is significantly changed after phase shift (dispersion). While using eight steps for phase stepping, the calculated phase shift is 0.125π±0.002π for the monochromatic spectrum and 0.142π±0.047π for the polychromatic spectrum, where the uncertainty is about 30% due to dispersion. That is another source of noise in the retrieved DPC images.

In experiments we cannot directly observe the fringe contrast of a self-image. Instead, we can estimate the fringe contrast from the phase-stepping images acquired at each phase step because the background intensity represents a point on the solid curve in Figures FIGS. 15A and 15B. Such a contrast is only 1.20 vs. 0.70 (normalized) for our bench-top system. Despite the imperfectness of gratings, the low fringe contrast due to polychromaticity is a major reason why the actual x-ray dose is much higher than expected.

DPC-CBCT imaging process was simulated for each energy channel using the numerical phantom as described above to produce a series of spectral DPC-CBCT reconstructions. A polychromatic DPC-CBCT reconstruction was also simulated by summing up all the energy channels after Fresnel diffraction, as suggested by Equations (1) and (2).

The reconstructed axial images are shown in FIGS. 16A-16E. FIGS. 16A-16D are reconstructions from four energy channels, which are respectively 20 keV, 30 keV, 40 keV and 45 keV. FIG. 16E is the reconstruction using the combined polychromatic spectrum. Judging by visual inspection, the four spectral DPC-CBCT reconstructions show different noise levels, uniformity and contrast levels. The reconstruction at 30 keV, which is the optimal energy, looks comparable to that from the polychromatic DPC-CBCT reconstruction.

The measured central noise level, uniformity and contrasts of the four inserts are listed in Table 6 in the unit of CT Numbers (CTN). It should be noted that at 30 keV, where the system is optimized, the channel is able to provide the lowest noise level and the highest object contrast, and the overall image quality is similar to that for the polychromatic DPC-CBCT using the entire spectrum. While other energy channels provide sub-optimal noise and contrast, they still provide significant information of the energy response of the phase coefficient for each insert, which directly leads to a potential “coloring” representation of objects and helps improved diagnostic efficiency and accuracy.

TABLE 6 Image quality comparison of spectral DPC-CBCT and polychromatic DPC-CBCT Spectral DPC-CBCT Polychromatic 20 keV 30 keV 40 keV 45 keV DPC-CBCT Uniformity 163 40 52 44 46 (CTN) Noise (CTN) 12 8 17 43 9 Contrast (B) 46 52 43 37 50 (CTN) Contrast (C) 96 108 85 77 104 (CTN) Contrast (D) 137 148 131 128 142 (CTN) Contrast (E) 184 192 172 167 187 (CTN)

How to use and represent the multi-folded spectral information is another interesting topic for spectral imaging. For example, material decomposition is used for dual-energy CT to utilize the spectral information. For spectral DPC-CBCT imaging, a straightforward approach is to weight and sum up the reconstruction images obtained from all energy channels and to display the final images in conventional gray scales. FIGS. 17A and 17B show two examples of this representation. FIG. 17A is the weighted average by the inverse of reconstruction noise using ( 1/12, ⅛, 1/17, 0) where 12 CTN, 8 CTN and 17 CTN are the reconstruction noise at channel 20 keV, 30 keV and 40 keV. The purpose of this type of average is to reduce the noise in the final image, which is now only 6 CTN. FIG. 17B is the subtraction of the DPC-CBCT reconstructions from 30 keV and 40 keV, and thus the weighting coefficients are (0, 1, −1, 0). The purpose of this type of average is to enhance the difference of phase coefficients between certain energy channels.

An alternative coloring representation approach is proposed that displays an object using a color map, where each color component (Red, Green and Blue) is defined as the weighted sum of composite object information. For example, if there are four energy channels and the phase coefficients computed for each channel is φ₁, φ₂, φ₃ and φ₄, the RGB components can be are defined in Equation (4): (R,G,B)^(T) =W·(φ₁,φ₂,φ₃,φ₄)^(T)  (4) where w_(ij) are weighting factors to define each color component in display. The calculated RGB components can be used to represent a “color” imaging of the object that include all the spectral phase information. As an example, if a weighting matrix

$W = \begin{bmatrix} 0.8 & 0 & 0 & 0 \\ 0 & 1.0 & 0 & 0 \\ 0 & 0 & 0.6 & 0 \end{bmatrix}$

is used, the resulting image is shown in FIG. 18, where the difference of colors can further enhance some contrast features of the object.

To emphasize the main idea of this invention, the keys to successful implementations of all the eight embodiments concern a more efficient utilization of x-ray energy and dose. A method to generate a quasi-monochromatic spectrum is proposed for the DPC-CBCT imaging chain, which corresponds to the first, the second, the fifth and the sixth preferred embodiments. In addition, a method to obtain the spectral information of an object using the DPC-CBCT system is proposed as well, which corresponds to the third, the fourth, the seventh and the eighth preferred embodiments.

While preferred embodiments and variations thereon have been disclosed above, those skilled in the art who have reviewed the present disclosure will readily appreciate that other embodiments can be realized within the scope of the invention. For example, numerical values are illustrative rather than limiting. Also, any suitable technique or materials for manufacturing the grating can be used. Furthermore, the utility of the present invention is not limited to breast imaging, but instead can be applied to any biological or non-biological imaging. Therefore, the present invention should be construed as limited only by the appended claims. 

We claim:
 1. A method of cone beam CT imaging of a human breast without penetrating the chest cavity of a patient, comprising: acquiring projection images of the breast taken at different view angles by using a polychromatic x-ray source irradiating the breast but not the chest cavity with primary radiation, an energy-resolving detector having a plurality of energy channels, and a grating system; said acquiring comprising acquiring, for each of the plurality of energy channels of the detector, a respective plurality of the projection images of the breast taken at different view angles; performing three-dimensional (3D) computed tomography reconstructions of the breast for each of the plurality of energy channels to produce a respective plurality of differential phase contrast 3D reconstruction images; and combining the plurality of differential phase 3D reconstruction images to thereby produce one or more output images of the breast; wherein said combining of the plurality of differential phase 3D reconstruction images comprises assigning different weights to the images being combined.
 2. The method of claim 1, wherein said combining of the plurality of differential phase 3D reconstruction images comprises assigning different colors to the images being combined.
 3. The method of claim 2, wherein the assigning of different colors comprises applying a two-dimensional matrix of color weighting coefficients to the images being combined.
 4. The method of claim 1, wherein the combining produces the output image comprising three-dimensional (3D) matrix of attenuation coefficients of breast tissue voxels.
 5. The method of claim 1, wherein the combining produces an output image comprising a three-dimensional (3D) matrix of phase coefficients of breast tissue voxels.
 6. The method of claim 1, including stepping a source grating, which is between the x-ray source and the breast, to vary the spacing of the source grating from the x-ray source for different portions of said acquisition.
 7. The method of claim 6, wherein the stepping comprises moving the source grating linearly along an imaging x-ray beam from the source irradiating the breast.
 8. The method of claim 6, wherein the stepping comprises moving, to a different position between the x-ray source and the breast for different portions of said acquisition, a source grating mounted on a respective branch of a multi-branch source grating mechanism.
 9. The method of claim 8, wherein the stepping comprises rotating the multi-branch source grating mechanism about an axis along a propagation direction of the imaging x-ray beam.
 10. The method of claim 1 in which the grating system comprises a phase grating and an analyzer grating that are between the breast and the detector, and said acquiring comprises acquiring the projection images while the phase and analyzer grating are misaligned to thereby produce a Moire pattern at the detector.
 11. The method of claim 1, further comprising the following steps carried out before said acquiring of the projection images with the polychromatic source: imaging the breast using a different imaging modality to determine a region of interest in the breast; and selecting a relative position between an imaging beam from the polychromatic x-ray source and the breast determined by said region of interest and then carrying out the steps recited in claim
 1. 12. The method of claim 11 in which the different imaging modality is CT imaging other than differential phase imaging.
 13. The method of claim 1, wherein the combining of the 3D reconstruction images comprises producing a combined image resolving sub-micron structures in the breast.
 14. A breast CT system imaging a human breast with an x-ray imaging beam without penetrating the chest cavity of a patient with primary radiation, comprising: a projection image acquisition gantry a polychromatic x-ray source configured to irradiate the breast but not the chest cavity of a patient with an imaging beam of x-rays rotating around the breast, an energy-resolving detector configured to receive the imaging beam after passage thereof through the breast, and a grating system; said detector being configured to acquire, for each of the plurality of energy channels, a respective plurality of the projection images of the breast taken at different view angles; a computer processor configured to apply computer algorithms to the projection images and produce a respective differential phase 3D reconstruction image of the breast for each of the plurality of energy channels; and said computer processor being further configured to combine the plurality of differential phase 3D reconstruction images to thereby produce one or more output images of the breast; and a computer display configured to display the one or more of the output images of the breast; wherein said computer processor is configured to combine the plurality of differential phase 3D reconstruction images in a process that includes assigning different weights to the images being combined.
 15. The system of claim 14, wherein said computer processor is configured to combine the plurality of differential phase 3D reconstruction images in a process that includes assigning different colors to the images being combined.
 16. The system of claim 15, wherein the computer processor is configured to assign the different colors by applying a two-dimensional matrix of color weighting coefficients to the images being combined.
 17. The system of claim 14, wherein the computer processor is configured to produce an output image that is a three-dimensional (3D) matrix of attenuation coefficients of breast tissue voxels.
 18. The system of claim 14, wherein the computer processor is configured to produce an output image that is a three-dimensional (3D) matrix of phase coefficients of breast tissue voxels.
 19. The system of claim 14, wherein the grating system comprises a stepping source grating that is between the x-ray source and the breast and is configured to vary the spacing between the source grating and the x-ray source for different portions of the rotation of the imaging beam of x-rays.
 20. The system of claim 19, wherein the grating system comprises a motorized drive configured to move the source grating linearly along the imaging x-ray beam to vary said spacing.
 21. The system of claim 19, wherein the source grating comprises a multi-branch arrangement of individual source grating configured to rotate around an axis of the imaging beam to thereby place a respective source grating at a respective different distance from the source for different portions of the rotation of the imaging beam around the breast.
 22. The system of claim 14, wherein the grating system comprises a phase grating and an analyzer grating that are between the breast and the detector and are misaligned to thereby produce a Moire pattern at the detector.
 23. The system of claim 14, further comprising an imaging system that is in addition to said gantry and is configured to image the breast using a different imaging modality to determine a region of interest in the breast, and wherein said gantry is configured to select a relative position between the imaging beam and the breast determined by said region of interest.
 24. The system of claim 23 in which the different imaging modality is CT imaging other than differential phase imaging.
 25. The system of claim 14, wherein the computer processor configured to combine the plurality of differential phase 3D reconstruction images to thereby produce one or more output images of the breast is further configured to produce an output image resolving sub-micron structures in the breast.
 26. A method of cone beam CT imaging of an object, comprising: acquiring projection images of the object taken at different view angles by using a polychromatic x-ray source irradiating the object with an imaging beam, an energy-resolving detector having a plurality of energy channels receiving the imaging beam after passage thereof through the object, and a grating system; said acquiring comprising acquiring, for each of the plurality of energy channels of the detector, a respective plurality of the projection images of the object taken at different view angles; performing three-dimensional (3D) computed tomography reconstructions of the object for each of the plurality of energy channels to produce a respective plurality of differential phase contrast 3D reconstruction images of the object; and combining the plurality of differential phase 3D reconstruction images to thereby produce one or more output images of the object; wherein said combining of the plurality of differential phase 3D reconstruction images comprises assigning different weights to the images being combined.
 27. The method of claim 26, wherein said combining of the plurality of differential phase 3D reconstruction images comprises assigning different colors to the images being combined.
 28. The method of claim 27, wherein the assigning of different colors comprises applying a two-dimensional matrix of color weighting coefficients to the images being combined.
 29. The method of claim 26, wherein the combining produces the output image comprising three-dimensional (3D) matrix of attenuation coefficients of object voxels.
 30. The method of claim 26, wherein the combining produces an output image comprising a three-dimensional (3D) matrix of phase coefficients of object voxels.
 31. The method of claim 26, including stepping a source grating, which is between the x-ray source and the object, to thereby vary the spacing of the source grating from the x-ray source for different portions of said acquisition.
 32. The method of claim 31, wherein the stepping comprises moving the source grating linearly along the imaging x-ray beam.
 33. The method of claim 31, wherein the stepping comprises moving, to a different position between the x-ray source and the object for different portions of said acquisition, a source grating mounted on a respective branch of a multi-branch source grating mechanism.
 34. The method of claim 33, wherein the stepping comprises rotating the multi-branch source grating mechanism about an axis of the imaging x-ray beam.
 35. The method of claim 26 in which the grating system comprises a phase grating and an analyzer grating that are between the object and the detector, and said acquiring comprises acquiring the projection images while the phase and analyzer grating are misaligned to thereby produce a Moire pattern at the detector.
 36. The method of claim 26, further comprising the following steps carried out before said acquiring of the projection images with the polychromatic source: imaging the object using a different imaging modality to determine a region of interest in the object; and selecting a relative position between the imaging beam from the polychromatic x-ray source and the object determined by said region of interest and then carrying out the steps recited in claim
 26. 37. The method of claim 36 in which the different imaging modality is CT imaging other than differential phase imaging.
 38. The method of claim 26, wherein the combining of the 3D reconstruction images comprises producing a combined image resolving sub-micron structures in the object. 